P53-DNA Recognition: Difference between revisions
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The distinct <scene name='Sandbox_Reserved_170/Arg248/2'>shape of the minor groove recognized by Arg248</scene> is due to a transition of the four A/T base pairs of the CATG core elements to a Hoogsteen base pairing geometry. Regions with Hoogsteen base pairs (green) <scene name='Sandbox_Reserved_170/Hg_helix/2'>decrease the diameter of the double helix</scene> compared to regions with Watson-Crick base pairs (blue). | The distinct <scene name='Sandbox_Reserved_170/Arg248/2'>shape of the minor groove recognized by Arg248</scene> is due to a transition of the four A/T base pairs of the CATG core elements to a Hoogsteen base pairing geometry. Regions with Hoogsteen base pairs (green) <scene name='Sandbox_Reserved_170/Hg_helix/2'>decrease the diameter of the double helix</scene> compared to regions with Watson-Crick base pairs (blue). | ||
The reason for this deformation of the double helix is the <scene name='Group:USC-LCHS/3kz8_ba_hoogsteencloseup/2'>base pairing geometry in Hoogsteen base pairs</scene> with the approximately 180 degree rotation of adenine around the glycosidic bond and formation of hydrogen bonds with thymine at a different edge of the adenine compared to <scene name='Group:USC-LCHS/3kmd_wcbp_closeup/1'>standard Watson-Crick base pairing geometry</scene>. | The reason for this deformation of the double helix is the <scene name='Group:USC-LCHS/3kz8_ba_hoogsteencloseup/2'>base pairing geometry in Hoogsteen base pairs</scene> with the approximately 180 degree rotation of adenine around the glycosidic bond and formation of hydrogen bonds with thymine at a different edge of the adenine compared to <scene name='Group:USC-LCHS/3kmd_wcbp_closeup/1'>standard Watson-Crick base pairing geometry</scene>, depicted here for the identical base pair in a p53 response element with different sequence from [http://www.rcsb.org/pdb/explore.do?structureId=3KMD PDB ID# 3KMD]. | ||
=Further Reading= | =Further Reading= | ||
Hoogsteen base pairs have previously been found in protein-DNA complexes but usually associated with drastic deformations of the DNA. Only in one case of a homeodomain protein, a Hoogsteen base pair was identified in undistorted B-DNA <ref name=" | Hoogsteen base pairs have previously been found in protein-DNA complexes but usually associated with drastic deformations of the DNA. Only in one case of a homeodomain protein, a Hoogsteen base pair was identified in undistorted B-DNA <ref name="wolberger">Aishima J, Gitti RK, Noah JE, Gan HH, Schlick T, Wolberger C. A Hoogsteen base pair embedded in undistorted B-DNA. Nucleic Acids Res. 2002;30(23):5244-52.</ref>. | ||
As for p53-DNA recognition, Hoogsteen base pairs are not present in the complex with a different DNA sequence <ref name=" | As for p53-DNA recognition, Hoogsteen base pairs are not present in the complex with a different DNA sequence <ref name="chen">Chen Y, Dey R, Chen L. Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer. Structure. 2010;18(2):246-56.</ref> but the DNA undergoes a different deformation not observed in the complex with Hoogsteen base pairing. Since transient Hoogsteen base pairs have been detected in naked DNA with preferences for CA and TA dincucleotides<ref name="hashimi">Nikolova EN, Kim E, Wise AA, O'Brien PJ, Andricioaei I, Al-Hashimi HM. Transient Hoogsteen base pairs in canonical duplex DNA. Nature. 2011;470(7335):498-502.</ref>, the observation of the base pairing variant indicates a sequence-speific feature either recognized or stabilized by p53. | ||
A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69.</ref>.<br/> | A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69.</ref>.<br/> | ||
